Validation of Raised Cord Blood Interleukin-16 in Perinatal Asphyxia and Neonatal Hypoxic-Ischaemic Encephalopathy in the BiHiVE2 Cohort

O’Sullivan, Marc Paul; Sikora, K. M.; Ahearne, Caroline; Twomey, Deirdre; Finder, Mikael; Boylan, Geraldine B.; Hallberg, Boubou; Murray, Deirdre M.

doi:10.1159/000491386

Cited by 6 publications

(3 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies on cytokines in cord blood report that IL-6 and IL-16 have been elevated in newborns with HIE compared to controls [22–24]. We confirmed these results in our study.…”

Section: Discussionsupporting

confidence: 92%

Neuro-Specific and Immuno-Inflammatory Biomarkers in Umbilical Cord Blood in Neonatal Hypoxic-Ischemic Encephalopathy

Toorell,

Carlsson,

Hallberg

et al. 2023

Neonatology

Self Cite

View full text Add to dashboard Cite

Objectives: The aim of the study was to evaluate neuronal injury and immuno-inflammatory biomarkers in umbilical cord blood (UCB) at birth, in cases with perinatal asphyxia with or without hypoxic-ischemic encephalopathy (HIE), compared with healthy controls and to assess their ability to predict HIE. Study Design: In this case-control study, term infants with perinatal asphyxia were recruited at birth. UCB was stored at delivery for batch analysis. HIE was diagnosed by clinical Sarnat staging at 24 h. Glial fibrillary acidic protein (GFAP), the neuronal biomarkers tau and neurofilament light protein (NFL), and a panel of cytokines were analyzed in a total of 150 term neonates: 50 with HIE, 50 with asphyxia without HIE (PA), and 50 controls. GFAP, tau, and NFL concentrations were measured using ultrasensitive single-molecule array (Simoa) assays, and a cytokine screening panel was applied to analyze the immuno-inflammatory and infectious markers. Results: GFAP, tau, NFL, and several cytokines were significantly higher in newborns with moderate and severe HIE compared to a control group and provided moderate prediction of HIE II/III (AUC: 0.681–0.827). Furthermore, the levels of GFAP, tau, interleukin-6 (IL-6), and interleukin-8 (IL-8) were higher in HIE II/III cases compared with cases with PA/HIE I. IL-6 was also higher in HIE II/III compared with HIE I cases. Conclusions: Biomarkers of brain injury and inflammation were increased in umbilical blood in cases with asphyxia. Several biomarkers were higher in HIE II/III versus those with no HIE or HIE I, suggesting that they could assist in the prediction of HIE II/III.

show abstract

“…Previous studies on cytokines in cord blood report that IL-6 and IL-16 have been elevated in newborns with HIE compared to controls [22–24]. We confirmed these results in our study.…”

Section: Discussionsupporting

confidence: 92%

Neuro-Specific and Immuno-Inflammatory Biomarkers in Umbilical Cord Blood in Neonatal Hypoxic-Ischemic Encephalopathy

Toorell,

Carlsson,

Hallberg

et al. 2023

Neonatology

Self Cite

View full text Add to dashboard Cite

show abstract

“…of HIE in the primary study 65 40 59 62 Total mild HIE in the primary study 29 24 36 30 No. in the current study (mild HIE and EEG recording <6 hours of life) 9 16 19 14 Definition of mild HIE ≥1 abnormal finding on modified Sarnat Score at 24 hours of life but not meeting criteria for moderate or severe HIE Worst grade of encephalopathy in the first 24 hours using modified Sarnat Score but not meeting criteria for TH Worst grade of encephalopathy in the first 24 hours using modified Sarnat Score but not meeting criteria for TH 1 or more abnormal neurological finding on modified Sarnat Score at 1 hour of life but not meeting criteria for TH Exclusion from pooling (1) Infants who received TH ( n = 1) (1) Infants who received TH ( n = 4) (2) Other diagnosis than mild HIE (1) Infants who received TH ( n = 2) Main publications from cohorts to date Murray et al 57 Murray et al 58 Murray et al 59 Murray et al 30 Murray et al 23 Murray et al 15 Walsh et al 60 Walsh et al 61 Walsh et al 62 Walsh et al 63 Looney et al 64 O’Sullivan et al 65 Rennie et al 66 O’Sullivan et al 67 Finder et al 16 Pavel et al 68 TH therapeutic hypothermia, HIE hypoxic–ischaemic encephalopathy, GA gestational age, CPR cardiopulmonary resuscitation, PA perinatal asphyxia. a Exclusion from primary studies: infants <36 + 0 weeks’ gestation; known genetic disorders and/or inborn errors of metabolism; confirmed sepsis (positive blood or CSF cultures).…”

Section: Methodsmentioning

confidence: 99%

Multichannel EEG abnormalities during the first 6 hours in infants with mild hypoxic–ischaemic encephalopathy

et al. 2021

View full text Add to dashboard Cite

Background Infants with mild HIE are at risk of significant disability at follow-up. In the pre-therapeutic hypothermia (TH) era, electroencephalography (EEG) within 6 hours of birth was most predictive of outcome. This study aims to identify and describe features of early EEG and heart rate variability (HRV) (<6 hours of age) in infants with mild HIE compared to healthy term infants. Methods Infants >36 weeks with mild HIE, not undergoing TH, with EEG before 6 hours of age were identified from 4 prospective cohort studies conducted in the Cork University Maternity Services, Ireland (2003–2019). Control infants were taken from a contemporaneous study examining brain activity in healthy term infants. EEGs were qualitatively analysed by two neonatal neurophysiologists and quantitatively assessed using multiple features of amplitude, spectral shape and inter-hemispheric connectivity. Quantitative features of HRV were assessed in both the groups. Results Fifty-eight infants with mild HIE and sixteen healthy term infants were included. Seventy-two percent of infants with mild HIE had at least one abnormal EEG feature on qualitative analysis and quantitative EEG analysis revealed significant differences in spectral features between the two groups. HRV analysis did not differentiate between the groups. Conclusions Qualitative and quantitative analysis of the EEG before 6 hours of age identified abnormal EEG features in mild HIE, which could aid in the objective identification of cases for future TH trials in mild HIE. Impact Infants with mild HIE currently do not meet selection criteria for TH yet may be at risk of significant disability at follow-up. In the pre-TH era, EEG within 6 hours of birth was most predictive of outcome; however, TH has delayed this predictive value. 72% of infants with mild HIE had at least one abnormal EEG feature in the first 6 hours on qualitative assessment. Quantitative EEG analysis revealed significant differences in spectral features between infants with mild HIE and healthy term infants. Quantitative EEG features may aid in the objective identification of cases for future TH trials in mild HIE.

show abstract

“…28 In this study, to adjust for the differences between Irish and Swedish populations, a control population-based Z-score was created in place of the standardized mean and SD. 29 The 2-year outcome was considered normal if it did not fall one SD below the calculated control group mean in all three composite categories (cognitive, language, and motor). The outcome was considered abnormal if it fell one SD below the calculated control group mean in one or more of the three composite categories and severely abnormal if it fell two SD below the mean in at least one category.…”

Section: Neurodevelopmental Assessmentmentioning

confidence: 99%

Activin A and Acvr2b mRNA from Umbilical Cord Blood Are Not Reliable Markers of Mild or Moderate Neonatal Hypoxic–Ischemic Encephalopathy

et al. 2021

Self Cite

View full text Add to dashboard Cite

Background Activin A protein and its receptor ACVR2B have been considered viable biomarkers for the diagnosis of hypoxic–ischemic encephalopathy (HIE). This study aimed to assess umbilical cord blood (UCB) levels of Activin A and Acvr2b messenger RNA (mRNA) as early biomarkers of mild and moderate HIE and long-term neurodevelopmental outcome. Methods One-hundred and twenty-six infants were included in the analyses from the BiHiVE2 cohort, a multi-center study, recruited in Ireland and Sweden (2013 to 2015). UCB serum Activin A and whole blood Acvr2b mRNA were measured using enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively. Results Activin A analysis included 101 infants (controls, n = 50, perinatal asphyxia, n = 28, HIE, n = 23). No differences were detected across groups (p = 0.69). No differences were detected across HIE grades (p = 0.12). Acvr2b mRNA analysis included 67 infants (controls, n = 22, perinatal asphyxia, n = 23, and HIE, n = 22), and no differences were observed across groups (p = 0.75). No differences were detected across HIE grades (p = 0.58). No differences were detected in neurodevelopmental outcome in infants followed up to 18 to 36 months in serum Activin A or in whole blood Acvr2b mRNA (p = 0.55 and p = 0.90, respectively). Conclusion UCB Activin A and Acvr2b mRNA are not valid biomarkers of infants with mild or moderate HIE; they are unable to distinguish infants with HIE or infants with poor neurodevelopmental outcomes.

show abstract

Validation of Raised Cord Blood Interleukin-16 in Perinatal Asphyxia and Neonatal Hypoxic-Ischaemic Encephalopathy in the BiHiVE2 Cohort

Cited by 6 publications

References 44 publications

Neuro-Specific and Immuno-Inflammatory Biomarkers in Umbilical Cord Blood in Neonatal Hypoxic-Ischemic Encephalopathy

Neuro-Specific and Immuno-Inflammatory Biomarkers in Umbilical Cord Blood in Neonatal Hypoxic-Ischemic Encephalopathy

Multichannel EEG abnormalities during the first 6 hours in infants with mild hypoxic–ischaemic encephalopathy

Activin A and Acvr2b mRNA from Umbilical Cord Blood Are Not Reliable Markers of Mild or Moderate Neonatal Hypoxic–Ischemic Encephalopathy

Contact Info

Product

Resources

About